Table I.

Primary Immune Deficiencies with warts as a major feature

PID	Gene / protein mutated	Inheritance	Age at presentation of warts	Types / Location of warts	Other Infections	Other clinical associations	Immune phenotype
Epidermodysplasia Verruciformis	EVER1 and 2 / epidermodysplasia verruciformis 1 and 2	AR Reports of XL and AD	Infancy	Flat – trunk, neck, extremities Verrucous – sun exposed areas Hypo /hyper pigmented lesions resembling pityriasis versicolor		30-70% lesions undergo malignant transformation	+/-low T cells Low LPM Cutaneous anergy
WHIM	CXCR4 / chemokine receptor 4	AD	Variable	Flat, verrucous – extremities, trunk Verrucous - genital	Pneumonia, Cellulitis, Sinusitis, UTI, Thrombophlebitis, Omphalitis, Osteomyelitis, Soft tissue abscesses, HSV, VZV		Low IgG and IgA Normal IgM Normal antibody responses Neutropenia Low B cells Low CD27+ B cells Low IgD+ and IgD-B cells Low T cells Low LPA/LPM Cutaneous anergy
DOCK8	DOCK8 / DOCK8	AR	Variable	Flat, verrucous – trunk, face, extremities	S. aureus skin abscesses, Pneumonia, Sinusitis, Soft tissue infections, HSV, MCV, VZV	Eczema, Food allergies, Asthma, Lymphoreticular and squamous cell malignancies	High IgE Low IgM High or normal IgG High or normal IgA Eosinophilia +/-Low T cells Low B cells Low NK cells Variable antibody responses Low LPA/LPM
ICL	Unknown	?	Late adolescence, adult	Flat, verrucous – face, trunk, extremities Verrucous -genital	Opportunistic infections – MAC, Cryptococcus, histoplasmosis, Mucocutaneous Candida, HSV, P. Jirovecii rare	Autoimmune disease	CD4 <300 Low, normal, or high CD8+ T cells Normal or low B and NK cells Variable polysaccharide antibody response, Normal protein antibody response Variable T cell function
						Autoantibodies
						Mucocutaneous
						Squamous cell cancer
GATA2 deficiency	GATA2/GATA2 binding protein	AD	Late adolescence / adult	Flat, verrucous – face, trunk, extremities, disseminated, genital	NTM	Myelodysplasia, leukemias, Malignancy Panniculitis Thromboembolic phenomena Pulmonary alveolar proteinosis Lymphedema	Profound monocytopenia Low B cells Normal immunoglobulins Normal antibody responses Low NK cells Variable T cell counts Variable T cell function
MonoMAC					Histoplasma
DCML					Aspergillus
Emberger syndrome					Cryptococcus
					VZV
					HSV
Netherton Syndrome	SPINK5 / LEKTI	AR	Adolescence, adulthood	Common, plane – extremities, trunk Verrucous -genital	Cellulitis	Bamboo hair	High IgE Normal or high IgG Low CD4+ T cells Low LPM High C3 and C4
					Bacteremia	Icthyosis
					Cutaneous HSV	Eczema
						Food allergies
						Asthma
STK4 Deficiency	STK4 / STK4 or MST1	AR	Unknown	Cutaneous	Cellulitis	Autoimmunity	Low CD4+ T cells Low CD45RA+ T cells Low CD25+T cells Normal CD8+ T cells Mildly low B cells Low IgD+IgM+CD27+ B cells Low IgD-IgM-CD27+ B cells High CD38+IgM+ B cells Normal NK cells Neutropenia Absent LPM Abnormal antibody responses High IgG High or normal IgA and IgE
					Skin Abscesses	EBV related malignancy
					Pneumonia	Structural heart disease
					Sinusitis
					HSV
					VZV
					MCV
					EBV

AR, autosomal recessive; AD, autosomal dominant; XL, X-linked; LPM, lymphocyte proliferation to mitogen; WHIM, warts, hypogammaglobulinemia, infections, myelokathexis; UTI, urinary tract infection; HSV, herpes simplex virus; VZV, varicella zoster virus; Ig –G, -A, -M, -E, -D, immunoglobulin –G, -A, -M, -E, -D; LPA, lymphocyte proliferation to antigen; DOCK8, dedicator of cytokinesis 8; MCV, molluscum cantagiosum virus; ICL, Idiopathic CD4 lymphopenia; MAC, Mycobacterium avium complex; MonoMAC, monocytopenia, M. avium complex infection; DCML, dendritic cell, monocyte, B cell and NK cell lymphopenia; NTM, nontuberculous mycobacteria; SPINK5, serine protease inhibitor Kazal-type 5; LEKTI, lympho-epithelial Kazal-type related inhibitor; STK4, serine-threonine protein kinase 4; MST1, mammalian sterile 20-like protein; EBV, Epstein-Barr virus.